Bacteriophage self-counting in the presence of viral replication.
Bacteriophage self-counting in the presence of viral replication.
复制标题
病毒复制存在时噬菌体自我计数。
DOI：
10.1073/pnas.2104163118
复制
发表时间：
2021
影响因子：
11.1
通讯作者：
Igoshin,OlegA
中科院分区：
文献类型：
--
作者：
Yao,Tianyou;Coleman,Seth;Nguyen,ThuVuPhuc;Golding,Ido;Igoshin,OlegA
当宿主细胞丰度较低时，温和的噬菌体选择休眠(溶原性)感染。噬菌体lambda通过在较高的感染复数(MOI)下增加溶原性的频率来实施这一策略。然而，目前尚不清楚噬菌体如何可靠地计算感染病毒基因组，即使它们的细胞内数量因复制而增加。通过将理论建模与病毒拷贝数和基因表达的单细胞测量相结合，我们发现复制不仅没有阻碍Lambda的决定，反而促进了它的决定。在非复制型突变体中，病毒基因的表达只是随着MOI的变化而变化，而不是分化成裂解(毒力)和溶源的轨迹。在野生型噬菌体早期感染期间也遵循类似的模式。然而，在感染的后期，决定基因对病毒复制的调节将最初温和的基因表达差异放大为不同的轨迹。因此，复制确保了对单噬菌体感染和较高MOI下的溶原性的最佳决策。
When host cells are in low abundance, temperate bacteriophages opt for dormant (lysogenic) infection. Phage lambda implements this strategy by increasing the frequency of lysogeny at higher multiplicity of infection (MOI). However, it remains unclear how the phage reliably counts infecting viral genomes even as their intracellular number increases because of replication. By combining theoretical modeling with single-cell measurements of viral copy number and gene expression, we find that instead of hindering lambda’s decision, replication facilitates it. In a nonreplicating mutant, viral gene expression simply scales with MOI rather than diverging into lytic (virulent) and lysogenic trajectories. A similar pattern is followed during early infection by wild-type phage. However, later in the infection, the modulation of viral replication by the decision genes amplifies the initially modest gene expression differences into divergent trajectories. Replication thus ensures the optimal decision—lysis upon single-phage infection and lysogeny at higher MOI.